The effect of tetracaine on stimulated contractions, sarcoplasmic reticulum Ca2+ content and membrane current in isolated rat ventricular myocytes
Article first published online: 22 SEP 2004
The Journal of Physiology
Volume 507, Issue 3, pages 759–769, March 1998
How to Cite
Overend, C. L., O'Neill, S. C. and Eisner, D. A. (1998), The effect of tetracaine on stimulated contractions, sarcoplasmic reticulum Ca2+ content and membrane current in isolated rat ventricular myocytes. The Journal of Physiology, 507: 759–769. doi: 10.1111/j.1469-7793.1998.759bs.x
- Issue published online: 22 SEP 2004
- Article first published online: 22 SEP 2004
- (Received 20 August 1997; accepted after revision 12 November 1997)
- 1The effects of tetracaine were examined on rat ventricular myocytes. In both field-stimulated and voltage-clamped cells tetracaine (100–200 μM) produced an initial decrease of contraction before a recovery towards the control level. Removal of tetracaine produced a transient overshoot of contraction to levels greater than the control.
- 2The transient decrease of contraction produced by tetracaine was accompanied by a small transient increase in the integral of the L-type Ca2+ current and a larger transient decrease of the Na+-Ca2+ exchange current on repolarization. These are attributed to decreased systolic release of Ca2+. On removal of tetracaine there was an increase of the Na+-Ca2+ exchange current. Before the addition of tetracaine, calculated Ca2+ influx and efflux across the sarcolemma were approximately equal. On adding tetracaine, efflux was transiently less than influx and, on removal of tetracaine, efflux was greater than influx.
- 3These changes in Ca2+ fluxes result in an increase of cell Ca2+ during exposure to tetracaine. The calculated magnitude of this increase was equal to that measured directly by applying caffeine (20 mM) to release sarcoplasmic reticulum (SR) Ca2+ and integrating the resulting Na+-Ca2+ exchange current.
- 4It is concluded that the effects of tetracaine can be accounted for by depression of calcium-induced Ca2+ release (CICR). The response is transient because the inhibition is compensated for by an increase of SR Ca2+ content such that there is no steady-state effect on the magnitude of the systolic Ca2+ transient. The consequences of this result for the effects of other modulators of CICR are discussed.